Effect of Structure on Biological Mechanisms. The purines and pyrimidine nucleosides and nucleotides participate in biological processes as components of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), as substrates of various enzymes, and as components of numerous coenzymes. Suitably modified they are useful as drugs, especially antibiotics and are excellent tools for the study of many enzymatic reactions at the molecular level. Much of their effectiveness is connected with their tendency to assume favorable conformations. Circular Dichroism (CD) and N.M.R. are particularly effective tools in establishing the relatively stable conformation of these compounds. We are making definitive (CD) and (NMR) studies on the over one thousand compounds of this type at our disposal. Magnetic Circular Dichroism and absorption spectra supplement these studies. Successful quantum mechanical calculations of the relative potential energy minimal are proving helpful in establishing the favored conformations and our extended Huckel calculations are effective help in the interpretation of the absorption CD and MCD spectra. Spectral and quantum mechanical studies of various other compounds, such as the substituted benzenes, are helpful in calibrating our experimental and theoretical methods. Other studies of the degenerative diseases including cancer are directed to an investigation of the effect of the free radicals arising from both irradiation and the errors in metabolism in bringing about the mutations responsible for disease and in aging. The extensive statistical information on death from various causes in the different countries as it depends upon age and sex are being used in a quantitative effort to estimate the roles played by mutations in initiating such diseases as cancer and the effectiveness of the immune reactions in terminating the disease. Cooperation with members of the departments of physiology and anesthesiology has made possible experimental and theoretical investigations of general and local anesthesia. This is proving to be a highly informative and fruitful endeavor.